Mice of the SJL/J strain demonstrate a high incidence (90 percent at 13 months) of spontaneous reticulum cell sarcoma (RCS). It is the intent of this project to initiate studies which will establish the underlying genetic basis for this malignancy and, in so doing, determine the nature and the number of the genes involved. This will be accomplished by the application of Mendelian genetic principles to the rates of disease incidence in SJL/J and hybrid mice. Progress to date in the understanding of the disease process has been hindered by the multicellularity of the tumor and the lack of obvious association with murine leukemia virus expression. By breeding SJL/J mice with normal strains to produce F1 mice, the dominant or recessive nature of disease expression will be determined. Subsequent matings of F1 mice to parental strains will produce backcross mice in which the incidence of RCS will be dependent upon the number of independently segregating disease-associated genes. The number of these genes will be indicated by relative rates of RCS in SJL/J and backcross mice. Two loci in particular (Fv-1 and H-2) will be examined for their influence on RCS because of previously demonstrated effects of these genes on other murine lymphoreticular tumors. Mice of SJL/J backcross populations in which the normal parent is not H-2s will be typed by hemagglutination and followed for cosegregation of resistance to RCS with H-2 heterozygosity. Additionally, mice of SJL/J backcross populations in which the normal parent differs from SJL/J both at Fv-1 and the tightly-linked gene Gpd-1, will be Gpd-1 typed by starch gel electrophoresis and followed for cosegregation of resistance to RCS with Gp-1 (and hence Fv-1) heterozygosity.